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Byers posted an update 10 months, 3 weeks ago
Sodium oxybate (SMO) has been approved in Italy and Austria for the maintenance of abstinence in alcohol dependent (AD) patients. Although SMO is well tolerated in AD patients, cases of abuse and misuse have been reported outside the therapeutic setting. Here we report on a phase IIb double-blind, randomized, placebo-controlled trial for the maintenance of abstinence in AD patients with a new abuse and misuse deterrent formulation of SMO. A total of 509 AD patients were randomized to 12 weeks of placebo or one of four SMO doses (0.75, 1.25, 1.75 or 2.25 g t.i.d.) followed by a one-week medication-free period. The primary endpoint was the percentage of days abstinent (PDA) at end of treatment. An unexpectedly high placebo response (mean 73%, median 92%) was observed. This probably compromised the demonstration of efficacy in the PDA, but several secondary endpoints showed statistically significant improvements. A post-hoc subgroup analysis based on baseline severity showed no improvements in the mild group, but statistically significant improvements in the severe group PDA mean difference +15%, Cohen’s d = 0.42; abstinence risk difference +18%, risk ratio = 2.22. No safety concerns were reported. Although the primary endpoint was not significant in the overall population, several secondary endpoints were significant in the intent-to-treat population and post-hoc results showed that treatment with SMO was associated with a significant improvement in severe AD patients which is consistent with previous findings. New trials are warranted that take baseline severity into consideration.T cell dysfunction is a common characteristic in leukemia patients that significantly impacts clinical treatment and prognosis. However, the mechanism underlying T cell dysfunction and its reversal remains unclear. In this study, in accordance with our previous findings, we found that the expression of NFAT2 and pri-miR-17 ~ 92 are lower in peripheral blood CD3+ T cells from chronic myelogenous leukemia (CML) patients by gene expression analysis. We further demonstrate that the NFAT2-induced activation, differentiation, and expression of cytokines in human umbilical cord blood CD8+ naïve T cells are miR-20a-5p dependent. We also preliminarily explored the relationship between NFAT2 and miR-20a-5p in naive T cells. These results suggest that NFAT2 and miR-20a are crucial for regulating functional CD8+ T cells. Additionally, their alteration may be related to CD8+ T cell dysfunction in CML patients; thus, NFAT2 and miR-20a-5p may be considered potential targets for revising T cell function in leukemia immunotherapy.The silkworm (Bombyx mori) is an important economic insect that can be used as food in many countries in Asia. However, silkworms and their metabolites are an important source of allergens, which can induce severe allergic reactions. So far, there are no systematic studies on the potential allergens in silkworm and its metabolites. These studies have important guiding significance for the prevention, diagnosis, and treatment of silkworm allergy. The aim of this study was to identify the potential allergens from larva, pupa, moth, silk, slough and feces of silkworm and analyze the sequence homology of silkworm allergens with other allergens identified in the Allergenonline database. We have found 45 potential allergens in silkworm. The results of the homology comparison suggested that silkworm allergens likely cross-react with those of Dermatophagoides farinae, Aedes aegypti, Tyrophagus putrescentiae, Triticum aestivum and Malassezia furfur.Reservoirs are an important type of drinking water source for megacities, while lots of reservoirs are threatened by odor problems during certain seasons. The influencing factors of odor compounds in reservoirs are still unclear. During August 2019, a nationwide survey investigating the distribution of odor compounds in reservoirs used as drinking water sources was conducted on seven reservoirs. 2-methylisoborneol (2-MIB) and geosmin were detected in almost every reservoir, and some odor compound concentrations even exceeded the odor threshold concentration. The average concentration of 2-MIB was 2.68 ng/L, and geosmin was 3.63 ng/L. The average chlorophyll a concentration was 8.25 μg/L. The dominant genera of phytoplankton in these reservoirs belonged to cyanobacteria and diatom. Statistical analysis showed that odor compound concentration was significantly related to the chlorophyll a concentration and indicated that the odor compounds mainly came from phytoplankton. this website The concentration of odor compounds in the euphotic zone was significantly related to phytoplankton species and biomass. Therefore, the odor compound concentrations in the subsurface chlorophyll maxima layer was generally higher than in the surface layer. However, the odor compounds in the hypolimnion layer were related to the density current. This research suggests that both phytoplankton proliferation events and heavy storm events are important risk factors increasing odor compounds in reservoirs. Control of algal bloom, in-situ profile monitoring system and depth-adjustable pumping system will greatly reduce the risk of odor problems in reservoirs using as water supplies for large cities.Accumulation of organic pollutants in the environment calls for sensing physiological parameters adequate to indicate the presence of contaminants and their effects on ecosystems. Evidence points to the importance of insect adaptations in their habitats for the assessment of sensitive biomarkers so we examined the influence of origin and multigenerational adaptations of the Lymantria dispar larvae to chronic benzo[a]pyrene (B[a]P) treatment under laboratory conditions. The main aim was to compare reactions of larvae from unpolluted and polluted forests using alkaline phosphatase (ALP), acid phosphatase (ACP), and carboxylesterase (CE) specific activities in the midgut, including electrophoretic isoform patterns; midgut expression levels of Hsp70, larval development time (DT), and midgut mass (MM), after chronic exposure to 5 and 50 ng of B[a]P/g dry food weight. The biomarker potential of these parameters regarding larval pre-exposure history to pollution was estimated by principal component analysis (PCA). B[a]P treatment resulted in inhibition of ALP activity, a rise of CE activity, and reduction of MM in larvae from the unpolluted forest, while the population from the polluted forest showed significant elevation of Hsp70 expression in the midgut, prolonged DT, and reduction of MM.